Gertler J P, Perry L, L'Italien G, Chung-Welch N, Cambria R P, Orkin R, Abbott W M
Division of Vascular Surgery, Massachusetts General Hospital, Boston 02114.
J Vasc Surg. 1993 Dec;18(6):939-45; discussion 945-6.
Vascular procedures reoxygenate ischemic endothelial cells (EC) and arterialize saphenous vein (HSV) EC. The balance between the EC-derived fibrinolytic components, plasminogen activator (tPA), and plasminogen inhibitor (PAI-1) contributes to maintaining thromboresistance. This balance also affects proteolysis through plasmin generation, mediating matrix metabolism endothelial migration, angiogenesis, and theoretically affecting the development of intimal hyperplasia.
To explore the impact of varying oxygen tensions on EC fibrinolysis, HSV and human umbilical vein (HUV) were subjected to Po2 of 40 mm Hg for 24 hours with restoration of Po2 to 150 mm Hg for 24 hours. The tPA and PAI-1 antigen and tPA/PAI-1 antigen ratio in conditioned media (CM), expressed as increases or decreases % change, normalized for cell count, versus controls, were analyzed by enzyme-linked immunosorbent assay. Cellular tPA and PAI-1 mRNAs were assessed by Northern analysis.
The tPA but not PAI-1 was significantly decreased after the first 24 hours in HSVEC and significantly decreased after 48 hours in both HUVEC and HSVEC when compared with controls. Messenger RNA for tPA was unchanged but PAI-1 mRNA increased significantly for HSVEC and HUVEC after 24 hours of Po2 of 40 mm Hg, returning to baseline within 24 hours of Po2 to 150 mm Hg restoration.
These data support the hypothesis of a fibrinolytic shift after altered ambient O2 tensions exposure in endothelium and demonstrate that HSVEC are more sensitive to altered O2 tension than HUVEC. Altered O2 tensions depress EC fibrinolysis in this model.
血管手术可使缺血的内皮细胞（EC）重新获得氧供应，并使大隐静脉（HSV）内皮细胞动脉化。内皮细胞衍生的纤溶成分、纤溶酶原激活物（tPA）和纤溶酶原抑制剂（PAI-1）之间的平衡有助于维持抗血栓形成能力。这种平衡还通过纤溶酶的生成影响蛋白水解，介导基质代谢、内皮细胞迁移、血管生成，并在理论上影响内膜增生的发展。
为了探究不同氧张力对内皮细胞纤溶的影响，将HSV和人脐静脉（HUV）置于40 mmHg的氧分压下24小时，然后恢复到150 mmHg的氧分压24小时。通过酶联免疫吸附测定法分析条件培养基（CM）中tPA和PAI-1抗原以及tPA/PAI-1抗原比值，以相对于对照的增加或减少百分比变化表示，并根据细胞计数进行标准化。通过Northern分析评估细胞tPA和PAI-1 mRNA。
与对照相比，HSV内皮细胞（HSVEC）在最初24小时后tPA显著降低，而HUV内皮细胞（HUVEC）和HSVEC在48小时后tPA均显著降低。tPA的信使RNA未发生变化，但在40 mmHg氧分压24小时后，HSVEC和HUVEC的PAI-1 mRNA显著增加，在恢复到150 mmHg氧分压24小时内恢复到基线水平。
这些数据支持了内皮细胞暴露于改变的环境氧张力后纤溶发生转变的假说，并表明HSVEC比HUVEC对改变的氧张力更敏感。在该模型中，改变的氧张力会抑制内皮细胞纤溶。
